19056-83-8

Upstream product

• 87-13-8 diethyl 2-ethoxymethylenemalonate 
• 108-44-1 1-amino-3-methylbenzene 
• 226881-93-2 2-(2,2,2-trichloro-1-m-tolylamino-ethyl)-malonic acid diethyl ester 
• 99-08-1 1-methyl-3-nitrobenzene 
• 105-53-3 diethyl malonate 
• 27971-92-2 diethyl 2,2,2-trichloroethylidenepropanedioate 

Downstream Products

• 41460-18-8 ethyl 4-hydroxy-7-methylquinoline-3-carboxylate 
• 51726-77-3 4-hydroxy-7-methylquinoline-3-carboxylic acid 
• 144181-61-3 2,2,2-trifluoro-N-(2-hydroxy-5-methylphenyl)acetamide 
• 956485-77-1 C₃₉H₃₃NO₁₀ 
• 82121-08-2 4-hydroxy-7-methylquinoline 
• 63136-61-8 4-chloro-7-methyl-quinoline 
• 77721-00-7 ethyl 7-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylate 
• 50593-19-6 ethyl 4-chloro-7-methylquinoline-3-carboxylate 

Relevant academic research and scientific papers

Nitrogen-containing heterocyclic compound as well as preparation method, pharmaceutical composition and application thereof

The invention provides a nitrogen-containing heterocyclic compound as well as a preparation method, a pharmaceutical composition and application thereof, and particularly provides a compound as shownin a formula I which is described in the specification,

3-(Benzo[: D] thiazol-2-yl)-4-aminoquinoline derivatives as novel scaffold topoisomerase i inhibitor via DNA intercalation: Design, synthesis, and antitumor activities

Twenty-seven 3-(benzo[d]thiazol-2-yl)-4-aminoquinoline derivatives have been designed and synthesized as topoisomerase I inhibitors. The in vitro anti-proliferation evaluation against four human cancer cell lines (MGC-803, HepG-2, T24, and NCI-H460) and one normal cell line (HL-7702) indicated that most of them exhibited potent cytotoxicity. Among them, 5a was identified as the most promising candidate with a low IC50 value of about 2.20 ± 0.14 and was selected for further exploration. Spectroscopic analyses and agarose-gel electrophoresis assays indicated that 5a could interact with DNA and strongly inhibit topoisomerase I (Topo I). Further screening of the Topo I activity of compounds 5b, 5c, 5e, 5f, 5h, 5i, 5j, 5l, and 5n suggested that some of the compounds might exert quite a different cytotoxicity profile to that of 5a. Molecular modeling studies confirmed that 5a adopts a unique mode to interact with DNA and Topo I. Other molecular mechanistic studies suggested that the treatment of MGC-803 cells with 5a induces S phase arrest, up-regulates the pro-apoptotic protein, down-regulates the anti-apoptotic protein, activates caspase-3, and subsequently induces mitochondrial dysfunction so as to induce cell apoptosis. The in vivo efficiency of 5a was also evaluated on MGC-803 xenograft nude mice and the relative tumor growth inhibition was 42.4percent at 12 mg kg-1 without an obvious loss in the body weight. This journal is

Structural development of a type-1 ryanodine receptor (RyR1) Ca2+-release channel inhibitor guided by endoplasmic reticulum Ca2+ assay

Type-1 ryanodine receptor (RyR1) is a calcium-release channel localized on sarcoplasmic reticulum (SR) of the skeletal muscle, and mediates muscle contraction by releasing Ca2+ from the SR. Genetic mutations of RyR1 are associated with skeletal muscle diseases such as malignant hyperthermia and central core diseases, in which over-activation of RyR1 causes leakage of Ca2+ from the SR. We recently developed an efficient high-throughput screening system based on the measurement of Ca2+ in endoplasmic reticulum, and used it to identify oxolinic acid (1) as a novel RyR1 channel inhibitor. Here, we designed and synthesized a series of quinolone derivatives based on 1 as a lead compound. Derivatives bearing a long alkyl chain at the nitrogen atom of the quinolone ring and having a suitable substituent at the 7-position of quinolone exhibited potent RyR1 channel-inhibitory activity. Among the synthesized compounds, 14h showed more potent activity than dantrolene, a known RyR1 inhibitor, and exhibited high RyR1 selectivity over RyR2 and RyR3. These compounds may be promising leads for clinically applicable RyR1 channel inhibitors.

Quinolone-Hydroxyquinoline Tautomerism in Quinolone 3-Esters. Preserving the 4-Oxoquinoline Structure To Retain Antimalarial Activity

Recent publications report in vitro activity of quinolone 3-esters against the bc1 protein complex of Plasmodium falciparum and the parasite. Docking studies performed in silico at the yeast Qo site established a key role for the 4-o

Structure-activity relationships for ferriprotoporphyrin IX association and β-hematin inhibition by 4-aminoquinolines using experimental and ab initio methods

In order to probe structure-activity relationships of association with ferriprotoporphyrin IX (log K) and inhibition of β-hematin formation, a series of 4-aminoquinolines with varying substituents at the 7-position (X) have been synthesized. These have been further elaborated by introduction of two different R groups on the 4-amino nitrogen atom in the form of methyl (R = Me) and ethylamine (R = EtNH2) side chains. Data for a previously investigated series containing an N,N-diethyl-ethylamine side chain were also compared with the findings of this study. Experimentally, log K values for the simple 4-aminoquinoline series (R = H) were found to correlate with the hydrophobicity constant (π) of the group X. The log K values for the series with R = Me and EtNH2 were found to correlate with those of the series with R = H. The log of the 50% β-hematin inhibitory activity (log BHIA50) was found to correlate with log K and either meta (σm) or para (σp) Hammett constants for the series with R = Me and EtNH2, but not the simple series with R = H. To further improve predictability, correlations with ab initio electrostatic parameters, namely Mulliken and CHelpG charges were investigated. The best correlations were found with CHelpG charges which indicated that log K values can be predicted from the charges on atom H-8 and the group X in the quinolinium species computed in vacuum, while log BHIA50 values can be predicted from the CHelpG charges on C-7, C-8 and N-1 for the neutral species in vacuum. These correlations indicate that association and inhibition of β-hematin formation are separately determined. They also suggest that electron withdrawing groups at the 7-position, but not necessarily hydrophobic groups are required for hemozoin inhibition. The upshot is that the correlations imply that considerably more hydrophilic hemozoin inhibitors are feasible.

Molecular design, synthesis and biological evaluation of 1,4-dihydro-4-oxoquinoline ribonucleosides as TcGAPDH inhibitors with trypanocidal activity

The 1,4-dihydro-4-oxoquinoline ribonucleoside, Neq135, is the first low micromolar trypanosomatidae inhibitor to show good ligand efficiency (0.28 kcal mol-1 atom-1) and good ligand lipophilicity efficiency (0.37 kcal mol-1/sup

Oxoquinoline acyclonucleoside phosphonate analogues as a new class of specific inhibitors of human immunodeficiency virus type 1

The emergence of a multidrug-resistant HIV-1 strain and the toxicity of anti-HIV-1 compounds approved for clinical use are the most significant problems facing antiretroviral therapies. Therefore, it is crucial to find new agents to overcome these issues. In this study, we synthesized a series of new oxoquinoline acyclonucleoside phosphonate analogues (ethyl 1- [(diisopropoxyphosphoryl)methyl]-4-oxo-1,4-dihydroquinoline-3-carboxylates 3a-3k), which contained different substituents at the C6 or C7 positions of the oxoquinoline nucleus and an N1-bonded phosphonate group. We subsequently investigated these compounds' in vitro inhibitory effects against HIV-1-infected peripheral blood mononuclear cells (PBMCs). The most active compounds were the fluoro-substituted derivatives 3f and 3g, which presented excellent EC 50 values of 0.4 ± 0.2 μM (3f) and 0.2 ± 0.005 μM (3g) and selectivity index values (SI) of 6240 and 14675, respectively.

Design, synthesis, and biological evaluation of novel quinoline derivatives as HIV-1 Tat-TAR interaction inhibitors

Thirty-two quinoline derivatives were designed and synthesized as HIV-1 Tat-TAR interaction inhibitors. All the compounds showed high antiviral activities in inhibiting the formation of SIV-induced syncytium in CEM174 cells. Nine of them with low cytotoxicities were evaluated by Tat dependent HIV-1 LTR-driven CAT gene expression colorimetric enzyme assay in human 293T cells, indicating effective inhibitory activities of blocking the Tat-TAR interaction. Molecular modeling experiments indicated that these compounds may inhibit Tat-TAR interaction by binding to Tat protein instead of TAR RNA.

Synthesis and anti-HSV-1 activity of quinolonic acyclovir analogues

Several 1-[(2-hydroxy-ethoxy)methyl]-3-carbethoxy-4(1H)quinolones (2a-l) and l-[(2-hydroxy-ethoxy)methyl]-4(1H)quinolone-3-carboxylic acids (3a-j and 3l) were synthesized and 2a-j, 2l and 3a-j, 3l were evaluated against herpes simplex virus type 1 (HSV-1), employing a one-pot reaction: silylation of the desired quinolone (BSTFA 1% TMCS) followed by equimolar amount addition of 1,3-dioxolane, chlorotrimethylsilane and KI, at room temperature. The acyclonucleosides 2a-l were obtained in 40-77% yields. The esters 2a-j and 2l were subsequently converted into the corresponding hydroxyacids 3 in 40-70% yields. Attempts of hydrolysis of 2k produced only a mixture of degradation products. Antiviral activity of 2 and 3 on HSV-1 virus infection was assessed by the virus yield assay. Except for compounds 2i and 3e, the acyclonucleosides were found to reduce the virus yield by 70-99% at the concentration of 50 μM, being the acids, in general, more effective inhibitors than their corresponding esters. Compounds 3j and 2d exhibited antiviral activity against HSV-1 virus with EC50 of 0.7 ± 0.04 and 0.8 ± 0.09 μM, respectively. Both compounds were not toxic towards the Vero cell line.

Synthesis of selected novel covalently linked flavoquinolones

The synthesis of novel covalently linked flavoquinolones via amide bond is described using mixed anhydride method and their spectroscopic studies have been done by UV/Vis and 1H NMR spectroscopic data. Georg Thieme Verlag Stuttgart.